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Prior to my current post, I’d not given too much thought to scale up. I suspect to the majority of early career synthetic chemists, “large-scale” is synonymous with breaking out the one-liter round bottom flask. That’s pretty much the comfortable upper bound of what you can work with 1) on a benchtop; 2) with magnetic stirring; and 3) with a oil bath heat source.

Your efforts on this scale will yield somewhere in the ballpark of 100 grams of product, depending on formula weight and a slew of other variables. And what’s more, purification and workup has now ventured into the realm of things that are no longer routine. A one-liter reaction volume is going to require a rather large separatory funnel (as a side note, Chemglass sells them up to 22-L — good luck with that). And unless your starting materials and product have wildly different silica affinities, you’re going to have quite a bit of fun trying to run a 100-gram flash column, so you’ll likely have to break it into a couple runs.

And that’s all great until you need to crank out a kilogram of material. You can now forget about running things in round bottomed flasks (Chemglass also sells a 22-L round bottomed flask, a testament to the age-old adage “just because you can does not mean you should“). You’re also not going to have much luck trying to fit a vessel that size onto a hot plate, so that rules out both magnetic stirring (which would be ineffective anyway) and conventional heating baths or mantles.

Things like efficient mixing and heat transfer — which we hand wave away at the gram-scale — start to matter quite a bit once you cross the kilogram threshold. So you’re going to need a specialized, jacketed reactor, through which you can recirculate a heated (or cooled) thermal transfer media. And because surface area to volume ratios are the way they are, the temperature gradient between the outside of the reactor and the inside can be pretty dramatic. So you’ve really got to get things mixed well, which means you need motorized stirring and a decent sized impeller.

Next on your synthetic checklist is workup, which now takes an entire day in and of itself. Pray you don’t need to purify anything chromatographically. Your precipitation that required 10 ml of solvent X per ml solvent Y suddenly won’t fit in any container in the lab, save the 55-gallon waste drum. I’m not ashamed to admit I’ve MacGyvered a workup involving a 5-gallon orange Home Depot paint bucket at a previous position.

All this, and I haven’t even touched on time yet. Everything at the kilo-scale takes longer. A reaction which you could comfortably set up in 20 minutes at the gram scale will take you all morning to get going. And you’d best triple check your work here, as mistakes on this scale are costly.

Of course, the proper process chemists will scoff at the struggles of the kilo-scale. Steel reactors replace glass, drum evaporators replace rotavaps, and somehow I doubt the tried and true paint bucket workup would pass cGMP muster.

It’s remarkably difficult to parse my personal feelings about my country and the democratic process with the fact that half of my countrymen observed exactly what I did and reached the opposite conclusion.

As a scientist, I look at data for trends and use what I observe to reach conclusions. I like to think I’ve gotten pretty good at doing this. The apocalyptic hellscape repeatedly described by DJT is not one that really exists. This is borne out in the data – crime is on the decline, the economy is growing – things are getting better. The conclusion I drew from the last eight years of data is the trajectory we are on is fine. Perfect? No. But incremental improvements were making it better all the time. For everyone.

As a human being, I look at things said and done by each candidate and determine how they mesh with my worldview. It’s hard to know if I’m particularly good at this. Trump’s political brand is one of exclusion, and fear.

Exclusion and fear are not American values. It is a difficult day to be optimistic. I do not feel very American.

It’s been awhile since I’ve posted anything here — apologies. Lots has been going on as of late. The most significant news is that after much consideration, I have vacated my old position and switched gears to some new science at a smaller company. Readers of the blog will remember I’ve spent the better portion of the last three years working on, and blogging about, explosives.

Now I’m at a biotechnology startup, still doing chemistry — albeit completely different chemistry. I’m not entirely certain the direction I’m going to take this blog, although I do plan on updating more frequently.

I’ve also decided the blog name was getting a bit stale; “The Unemployed Chemist’ was a holdover name from when I was actually unemployed and looking to break into the field post graduation. So without further ado, let me welcome you to Benchtop Thoughts. And if you’re stuck in your ways, don’t worry, as the old URL will still redirect here.

I received an interesting email over the weekend from the founder of “a DIY scholarly publishing platform” (full text below).

Some of what the folks at The Winnower are proposing sounds familiar: there are inherent problems with the current model of scientific publishing. What stuck out a bit to me is the idea of assigning DOI’s to blog posts. While I don’t see posting original research to blogs happening any time soon, perhaps the post-peer-review format of blogging could benefit from some more structure.

As some of my readers know, a few months ago I was asked to pen the Blogroll column for the February publication of Nature Chemistry. The column was published at the end of January both in print and online. Stuart Cantrill, Nature Chemistry’s chief editor, posted the column to the Nature Chemistry Blog The Sceptical Chymist where you can read it for free. If you like fancy-looking PDFs as much as I do, and have institutional access, you can download the article ($) here.

In my column, titled “The bad and the ugly,” I write about misinformation in science, be it in popular culture, advertising, or the press. It’s short, and, in my opinion, worth a read.

I apologize for my prolonged radio-silence. It’s been a turbulent couple of months since I accepted my new synthetic chemistry position! I’ve been thinking quite a bit about this blog, and the direction I want to take it in from here on out. Up until now, I’ve been writing about whatever chemistry related topic I happen to find interesting.

But I got to thinking: I’m in a new role, working on complex synthetic problems outside my normal element. This blog fell somewhere between drug-synthesis (a topic already covered quite adequately by blogger Derek Lowe) and “pop-culture” chemistry. But now I’ve got this exiting new frontier of energetics and applied synthetic chemistry to talk about, from the inside.

Now I can talk about some interesting and under-reported chemistry related to weapons and explosives (maybe some drugs, too): all the stuff your mother told you to stay away from.